Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
PLoS One. 2011 May 10;6(5):e19764. doi: 10.1371/journal.pone.0019764.
The early endosome acts as a sorting station for internalized molecules destined for recycling or degradation. While recycled molecules are sorted and delivered to tubular endosomes, residual compartments containing molecules to be degraded undergo "maturation" before final degradation in the lysosome. This maturation involves acidification, microtubule-dependent motility, and perinuclear localization. It is currently unknown how sorting and the processes of maturation cooperate with each other. Here, we show that fission of a tubular endosome triggers the maturation of the residual endosome, leading to degradation. Use of the dynamin inhibitor dynasore to block tubular endosome fission inhibited acidification, endosomal motility along microtubules, perinuclear localization, and degradation. However, tubular endosome fission was not affected by inhibiting endosomal acidification or by depolymerizing the microtubules. These results demonstrate that the fission of recycling tubules is the first important step in endosomal maturation and degradation in the lysosome. We believe this to be the first evidence of a cascade from sorting to degradation.
早期内涵体充当了分拣站，负责分拣内吞的分子，这些分子要么被回收，要么被降解。当被回收的分子被分拣并运送到管状内涵体后，残留的含有待降解分子的隔室在最终被溶酶体降解之前会经历“成熟”过程。这个成熟过程涉及酸化、微管依赖性运动和核周定位。目前尚不清楚分拣和成熟过程是如何相互协作的。在这里，我们发现管状内涵体的分裂触发了残留内涵体的成熟，导致降解。使用动力蛋白抑制剂 dynasore 阻断管状内涵体的分裂会抑制酸化、内涵体沿着微管的运动、核周定位和降解。然而，抑制内涵体酸化或微管解聚并不影响管状内涵体的分裂。这些结果表明，回收管的分裂是内涵体在溶酶体中成熟和降解的第一步。我们认为这是从分拣到降解的级联反应的第一个证据。
